A short history of cancer

Cancer occurrences have been noted throughout history as far back as 3000 BC. Much has been learnt about the disease since then and we have made great advances in treating patients. But as Sarah McKay writes, there is still much more to learn.

Cancer is not a modern malady. Fossilised bones and the mummies of Egypt show evidence of tumours, and a written description of cancer has been found in an Egyptian papyrus dating back to 3000 BC. The ancient surgical manuscripts describe eight cases of breast cancer and the scripts bleakly note, “There is no treatment.”

Such a bleak outlook is no longer the case for most cancers. Today in Australia, more than 60% of people diagnosed will live more than five years after diagnosis. And for some cancers, five-year survival rates are nearing 90%.

These statistics are thanks largely to the explosion in our understanding of cancer during the past 50 years. But in the immortal words of Isaac Newton who stated, “If I have seen further it is by standing on the shoulders of giants”—researchers of today also owe much to the scientists and doctors of the Renaissance and 18th and 19th centuries who laid the foundations of modern day epidemiology and cancer treatment.

Advances in understanding the causes of cancer

Hippocrates (460–370 BC), the father of medicine, is credited with coining the term carcinoma, and for hypothesising that cancer was caused by ‘an imbalance of the four humors’.

Throughout history, countless causes other of cancer have been proposed including: angering the gods, fermenting or acidic lymph, chronic irritation, trauma, and infection. These theories stood unchallenged until the Renaissance when Galileo and Newton began to use the scientific method, which laid the foundations for the modern scientific study of disease.

The 18th century saw the birth of cancer epidemiology when three insightful observations were made. Firstly, the high incidence of breast cancer in nuns compared to non-celibate women gave the first hint that hormones may play a role in cancer. Secondly, descriptions of cancer of the scrotum prevalent in London’s chimney sweeps led to public health measures to reduce a person’s cancer risk at work. And thirdly, a book was published linking tobacco use with cancer, which laid the foundations for the US Surgeon General’s 1964 warning that smoking caused lung cancer.

Fast forward nearly 200 years to 2012 and the World Health Organization’s International Agency for Research on Cancer (IARC) identified more than 100 chemical, physical, and biological carcinogens (agents that cause cancer by damaging DNA or disrupting cell metabolism).

The genetics of cancer

We now know that cancer is a disease caused by damaged DNA. In the 61 years since James Watson and Francis Crick solved the structure of DNA, giving the world the iconic double helix, the pace of change in the field of cancer genetics has been dizzying.During the 1970s, scientists discovered oncogenes (genes that cause cells to grow out of control and become cancer cells), and tumour suppressor genes (normal genes that when damaged cause cells to grow out of control, which can lead to cancer). DNA sequencing technology became so sophisticated and efficient that by the early 1990s the human genome project (a project devoted to decoding the entire genome) was proposed. Decoding that first genome involved thousands of DNA sequencing machines, cost several billion dollars, and took almost 15 years to complete.

By comparison, the DNA sequencing machines of today are fully automated and can generate 2‐300 billion bases of DNA sequence per run—equivalent to the genomes of 30 people—in just a few days with costs in the mere hundreds of dollars. Personalised medicine—sequencing a patient’s genome and tailoring a treatment program based on their particular genetic profile—shows inordinate promise for cancer patients.

A brief history of cancer treatment

Surgery

Humans have always performed surgery on one another. The Roman physicians knew that cancer could be treated with surgery, and remarked, “After excision, even when a scar has formed, none the less, the disease has returned”. But it was not until the discovery of anaesthesia and aseptic techniques that surgery became anything but a terrifying last resort for the cancer patient.

The first radical mastectomy to treat breast cancer was performed in 1880, but more conservative methods of cancer resection were not developed until the 1970s when the total mastectomy and later lumpectomy were shown to be just as effective for treating early breast cancer. The trend for removing less healthy tissue extended to treating bone and soft tissue cancers of the limbs without the need for amputation, and rectal cancer without the need for colostomy.

The late 20th century saw the development of lymph node biopsies, and fibre optic technology and advances in imaging have reduced the need for exploratory surgery, allowing for precise tumour localisation, biopsy and removal, and reducing the risk of postoperative side effects.

Radiation Therapy

The 1901 Nobel Prize in physics was awarded to Wilhelm Conrad Roentgen for his discovery of what he called the “X-ray”, with “x” being the algebraic symbol for an unknown quantity. The turn of the 20th century also saw Marie and Pierre Curie’s discovery of radium and polonium, and their coining of the word ‘radioactivity’. Remarkably, within a couple of years, two Russian skin cancer patients were successfully treated with radiation therapy. Radiation therapy remains a mainstay of modern cancer treatment.

Driven by computer and imaging technology, we’ve seen a game changing shift towards more precise, targeted radiation therapy during the past couple of decades. The development of intensity modulated radiation therapy (IMRT) and image guided radiation therapy (IGRT) means radiation beams can be matched to the shape of the tumour and delivered from several directions reducing side effects. For some cancers this provides cure rates equivalent to surgery.

Chemotherapy

The chemotherapy era began during World War II when it was discovered that soldiers exposed to nitrogen mustard (a compound of mustard gas) died because their bone marrow was destroyed. Subsequent research found it killed rapidly dividing cells (such as cancer cells) by destroying their DNA. Interfering with cell division by damaging DNA causes cells to commit suicide (apoptosis)—this remains the underlying principle of chemotherapy.

Despite advances in chemotherapy during the 1950s and 60s, surgery and radiotherapy continued to dominate oncology until it became clear that cure rates plateaued at about 33%. The realisation that chemotherapy could be used in conjunction with surgery and/or radiation (nowadays called adjuvant treatment) was pivotal in improving patient survival.

Today, chemotherapy is tailored to a cancer’s molecular profile, stage, response to previous treatments, and often to the patient’s specific genetic profile. Dozens of combinations of drugs are proven to improve patient survival.

Immunotherapy

In the 1850s, physicians noticed that tumours would occasionally shrink if they became infected. This led to the idea that the patient’s immune system could be harnessed to fight cancer cells. Progress in immunotherapy was slow until Cambridge scientists first synthesised antibodies in the 1970s. Antibody synthesis together with expanding knowledge of the immune system, eventually led to the development of modern immunotherapy protocols for cancer.

Modern day survival rates

Until the last few decades, cancer was a death-sentence. During the 1970s, only about one of two people diagnosed with cancer survived up to five years. Today, highly tailored, effective treatments target the genetics of each cancer, and each patient. For many cancers survival rates top 90%.

We have seen incredible success in cancers such as breast cancer, whose survival rates have risen from around 30% 30 years ago to about 80% today.

For rarer cancers, however, the outlook is still ‘bleak’. Brain cancer survival rates, for example, have barely changed in the last 30 years, and are as low as 5% for some forms. However, the revolutionary progress against other cancers shows us what is possible for the brain cancer patient of the future. The first sequencing of the human genome was a tour­-de-­force that was inconceivable just 20 years earlier. 10 years from now, brain cancer may be eminently survivable. As long as research funds are secured, we can expect brain cancer treatments to accelerate with a rate of change similar to that we have already witnessed. History teaches us that the future holds great promise.